Glaucoma (in particular, primary open-angle glaucoma) is one of the leading causes of blindness in the United States (Prevent Blindness America and the National Eye Institute, 2002). It produces a gradual and progressive degeneration of retinal ganglion cells, which transmit visual information along the optic nerve to the brain. Unfortunately, by the time this glaucomatous neuropathy is detected, there is typically extensive and permanent damage to the visual system and profound loss in visual function. There is evidence to indicate that select pathways of the visual system are affected in an early stage of the disease. Although glaucoma is often associated with elevated intraocular pressure, this is not always the case. Presently, there is a paucity of clinical screening and diagnostic tools available to vision professionals that aid in the early detection of this disease and in the monitoring of treatments for the purpose of neuroprotection.
The retina of the eye contains more than 130 million light-sensitive cells. These cells convert light into neural signals that are processed by a variety of neurons for certain features, and then transmitted via the optic nerve to the brain for interpretation. Birth defects, trauma from accidents, numerous kinds of disease, and age-related deterioration of the components of the eye can all contribute to visual disorders. Information processing in the brain is electrochemical in nature. Evoked potentials are the electrical responses of the brain elicited by sensory stimulation. The electrical responses of the brain produced by visual stimulation are visual evoked potentials. Alterations in the characteristic visual evoked potential indicate anomalies along the visual pathways.
Typically, the visual evoked potential (VEP) is measured from the scalp via surface electrodes while visual stimuli are displayed on a video monitor placed in front of the patient. When stimulation is applied to a particular sense of a human being, a corresponding brain potential is evoked at an information-processing part of the brain that functions to manage that particular sense. Visual evoked potentials can be used for diagnostic testing to assist physicians in the diagnosis of brain damage, diseases of the central nervous system, and diseases of the visual system in particular.
The visual evoked potential (VEP) is a noninvasive measure of cortical activity elicited by a visual stimulus. It is the sum of electrical signals conducted to the surface of the head and it is capable of providing quantitative information on the dynamics of the visual system. The manner in which the VEP is typically elicited, however, precludes the exploration of selective visual processes, and the manner in which the VEP is typically analyzed lacks efficiency and the rigor needed for its use as a pragmatic and objective tool. The subjectivity involved in the usual description of the VEP waveform has been a hindrance in all of its applications including the assessment of glaucoma. Thus, a potentially powerful tool for functional dissection of the visual pathways has been largely overlooked. Over the last several years, a number of stimulation and analysis techniques have been introduced to the field that provide the basis for an electrophysiological instrument that obviates these problems.
Hartline (1938) discovered the existence of ON and OFF cells in the visual system. ON and OFF cells originate at the first synapse in the retina, and they mediate the distinct perceptions of brightness (positive contrast) and darkness (negative contrast), respectively (Schiller, Sandell, & Maunsell, 1986). The ON pathway is particularly sensitive to disease processes involved in congenital stationary night blindness, muscular dystrophy, and glaucoma (Badr et al., 2003; Benoff et al., 2001; Fitzgerald et al., 1994; Greenstein et al., 1998).
Another important functional subdivision of the primary visual pathway was first discovered in the major relay station for visual processing in the brain, the lateral geniculate nucleus (LGN), but it too has its origin in the retina (Kaplan, Lee, & Shapley, 1990). The magnocellular (large cell) and parvocellular (small cell) layers of the LGN receive their inputs from M and P retinal ganglion cells, respectively. The morphological differences in these two types of cells produce quite different response characteristics. M cells are large in size and are highly sensitive to luminance contrast (respond to small differences in light level), whereas P cells are small in size and are relatively insensitive to luminance contrast. Both M and P pathways contain ON and OFF cells. Cells in the magnocellular and parvocellular layers of the LGN form synapses (make connections) in different sublayers of the primary visual cortex (the first visual processing center in posterior region of the brain), and synaptic activity occurring on parts of the neurons in this area is the principal source of the VEP. Evidence exists to indicate that the ON cells in the magnocellular pathway are particularly sensitive to and affected by disease processes such as muscular dystrophy (Benoff et al., 2001) and glaucoma (Greenstein et al., 1998; Badr et al., 2003).
Methods and systems exist for the detection of glaucoma using visual evoked responses (e.g., the multifocal VEP, Hood & Greenstein, 2003; behavioral measures obtained in visual field testing with conventional perimeters or frequency-doubling perimeters). However, the scientific principles, the stimuli used and the data processing methods in those techniques differ from the ones involved in the current invention.
In the prior art, a general VEP recording system was used in laboratories. The procedure of using this machine for visual neurophysiological studies is illustrated by flow chart 200 in FIG. 3. First at step 202, the user needs to configure the stimulus for parameters (e.g., spatial patterns, temporal frequency, contrast, luminance, number of repeated tests, etc.), and save the stimulus configuration in the system's computer. At step 204, a user enters the patient's information. Before starting the test, the user needs to select the pre-configured stimulus and the VEP data acquisition parameters (e.g., sampling rate in terms of the stimulus frequency and the frequency components in the VEP of interest to be extracted), at step 206. At step 208 the computer performs the test by displaying a stimulus to a patient and recording a VEP signal. At step 210 the computer saves VEP raw data to a hard disk. At step 212 the user has to determine if the test is complete. If the answer is no, the procedure goes back to step 206. If the answer is yes, then at step 214 (not automatically following step 212), the user has to take the stored VEP raw data and process the data with custom-made software to perform an assessment of visual function.